Acute myocardial infarction which results in the necrosis of cardiac muscle due to coronary artery occlusion is a disease with poor prognosis and is the main underlying condition for heart diseases which are the second cause of death in Japan. Existing therapies, acute phase catheterization and coronary artery bypass surgery, alleviate myocardial damage and contribute to the reduction of mortality rate; however, there are problems such as myocardial damage that occurs when the blocked coronary blood flow restarts (ischemia-reperfusion injury). Thus, development of further therapies is desired.
Recently, in basic experiments using animal models, bone marrow mesenchymal stem cell transplantation has been reported to suppress the development of myocardial infarction via regeneration of cardiac muscle by direct differentiation of the transplanted cells into constituent cardiac muscle cells, and also via suppression of left ventricular remodeling caused by the paracrine effect of the produced cytokines. Currently, clinical trials of autologous cell transplantations via various administration routes are being carried out. However, many issues remain to be resolved as problems concerning autologous cell transplantation, such as physical burden imposed at cell collection, cost and manpower involved in cell culturing, and the time required until cell transplantation. Meanwhile, it has been recently confirmed that a mechanism exists in which damaged tissue releases factors that recruit bone marrow pluripotent stem cells into blood to induce tissue regeneration at the damaged site. Tissue regeneration that uses the mechanism of inducing regeneration of damaged tissue in vivo by administering bone marrow stem cell-inducing factors is a non-conventional novel concept in regenerative therapy, and is believed to be advantageous compared to cell therapy that uses stem cells in that manpower is not required, stable supply is possible, and administration at an early stage of damage is possible.
In previous studies, the present inventors have identified the HMGB1 protein as a novel factor that mobilizes bone marrow pluripotent stem cells. HMGB1 is the major component of non-histone nuclear protein and is extracellularly released from dendritic cells, macrophages, or necrotic cells that accumulate in damaged sites, and is confirmed to be associated with various diseases.